Wenxi Yu1, Hongmei Zhang2, Jing Chen3, Xing Zhang4, Yong Chen5, Guofan Qu6, Gang Huang7, Yuhong Zhou8, Ting Ye3, Zhengfu Fan9, Yang Yao1. 1. Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China. 2. Department of Clinical Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. 3. Department of Bone Soft Tissue Oncology, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Department of Medical Melanoma and Sarcoma, Sun Yat-sen University Cancer Center, Guangzhou, China. 5. Department of Orthopaedic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. 6. Department of Orthopedics, Harbin Medical University Cancer Hospital, Harbin, China. 7. Department of Bone Neoplasms, Hunan Provincial Tumor Hospital, Changsha, China. 8. Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China. 9. Department of Orthopaedic Oncology, Beijing Cancer Hospital, Beijing, China.
Abstract
Background: Anti-angiogenic agents have been reported to exert promising clinical activity for advanced soft tissue sarcoma (STS). Apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, is effective and safe for various solid tumors, but its role in STS remains unclear. The aim of this study was to explore the efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory STS. Methods: In this multicenter, single-arm, phase 2 trial, patients aged 18-70 years with untreated or chemotherapy-refractory STS were enrolled and received 500 mg apatinib per day. During treatment, patients were followed up with imaging every 8 weeks. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were objective response rate (ORR), overall survival (OS), and adverse events (AEs), which were graded following the National Cancer Institute common terminology criteria for AEs version 4.03. Results: From June 2017 to October 2018, 53 patients were enrolled, 51 of whom received at least one dose of apatinib. Of the 53 patients, 41 (77.4%) had chemotherapy-refractory disease. The median follow-up was 13.3 months. The 6- and 12-month PFS rates were 46.8% and 25.2%, respectively, with a median PFS of 5.6 months [95% confidence interval (CI): 3.8-9.2 months]. The median PFS was 5.5 months for chemotherapy-refractory patients, 9.1 months for untreated patients, 13.9 months for patients with alveolar soft part sarcoma (ASPS), and 3.7 months for patients with clear cell sarcoma (CCS). The 12- and 24-month OS rates were 58.6% and 44.9%, respectively, with a median OS of 20.0 months (95% CI: 9.2-31.1 months). The median OS was 10.7 months for chemotherapy-refractory patients and not estimated for untreated, ASPS, nor CCS patients. In 50 evaluable patients, the ORR was 18.0% and the disease control rate was 86.0%. These results were similar to those of the per-protocol set. The most common grade 3 or 4 AEs included hypertension [30 (58.8%) of 51 patients], leukopenia [12 (23.5%)], proteinuria [8 (15.69%)], and hematuria [8 (15.69%)]. One patient died of unknown cause. Conclusions: This study suggested that apatinib might be effective and tolerable in patients with untreated or chemotherapy-refractory STS (NCT03064243). 2022 Annals of Translational Medicine. All rights reserved.
Background: Anti-angiogenic agents have been reported to exert promising clinical activity for advanced soft tissue sarcoma (STS). Apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, is effective and safe for various solid tumors, but its role in STS remains unclear. The aim of this study was to explore the efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory STS. Methods: In this multicenter, single-arm, phase 2 trial, patients aged 18-70 years with untreated or chemotherapy-refractory STS were enrolled and received 500 mg apatinib per day. During treatment, patients were followed up with imaging every 8 weeks. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were objective response rate (ORR), overall survival (OS), and adverse events (AEs), which were graded following the National Cancer Institute common terminology criteria for AEs version 4.03. Results: From June 2017 to October 2018, 53 patients were enrolled, 51 of whom received at least one dose of apatinib. Of the 53 patients, 41 (77.4%) had chemotherapy-refractory disease. The median follow-up was 13.3 months. The 6- and 12-month PFS rates were 46.8% and 25.2%, respectively, with a median PFS of 5.6 months [95% confidence interval (CI): 3.8-9.2 months]. The median PFS was 5.5 months for chemotherapy-refractory patients, 9.1 months for untreated patients, 13.9 months for patients with alveolar soft part sarcoma (ASPS), and 3.7 months for patients with clear cell sarcoma (CCS). The 12- and 24-month OS rates were 58.6% and 44.9%, respectively, with a median OS of 20.0 months (95% CI: 9.2-31.1 months). The median OS was 10.7 months for chemotherapy-refractory patients and not estimated for untreated, ASPS, nor CCS patients. In 50 evaluable patients, the ORR was 18.0% and the disease control rate was 86.0%. These results were similar to those of the per-protocol set. The most common grade 3 or 4 AEs included hypertension [30 (58.8%) of 51 patients], leukopenia [12 (23.5%)], proteinuria [8 (15.69%)], and hematuria [8 (15.69%)]. One patient died of unknown cause. Conclusions: This study suggested that apatinib might be effective and tolerable in patients with untreated or chemotherapy-refractory STS (NCT03064243). 2022 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
Soft tissue sarcoma (STS); angiogenesis; apatinib; neoplasm drug resistance
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